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Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Morphological changes of the splenic white pulp in athymic nude mice (nu/nu) and their normal littermates (nu/ + ) following intraperitoneal injection of bacterial lipopolysaccharide were studied by light and electron microscopy, immunofluorescence and autoradiography. Early blast formation and subsequent appearance of IgM-containing cells were observed by 72 h and at 120 h, respectively, in the periarteriolar sheath of nu/nu mice and in the follicular area of nu/ + mice. Ultrastructural details of blasts and the time course of their development were similar in both nu/nu and nu/ + mice. Lymphoblasts showed a large nucleus with a prominent nucleolus, many polysomes and poorly developed smooth endoplasmic reticulum. Plasmablasts had a nucleus with coarse heterochromatin and copious cytoplasm filled with dilated rough endoplasmic reticulum. Generally, lymphocytes proliferated and differentiated through lymphoblasts to plasmablasts by 72 h and finally to plasma cells at 120 h. However, this development was asynchronous since lymphoblasts, plasmablasts and plasma cells were observed simultaneously at 72 h. It was suggested that a B cell subset responsive to bacterial lipopolysaccharide matures to antibody-forming cells in the thymus-dependent area in nu/nu mice and in the thymus-independent area in nu/ + mice.
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PMID:In vivo maturation of B cells in the spleen of nude mice following administration of bacterial lipopolysaccharide. 34 Mar 88

Mouse spleen lymphoblasts induced with lipopolysaccharide and fetal calf serum were obtained in high yield and purity in their first proliferative cell cycle by floatation in dense bovine plasma albumin columns (3). The blasts were maintained in vitro for 3 more days. The cultures were examined in bulk on each day, and in addition, those cells in S phase initially were tagged with [(3)H]thymidine and followed continuously in vitro. Grain count dilution data indicated that most blasts divided but twice over a 2- to 3-day interval in vitro. [(3)H]Thymidine pulse radiolabeling and flow microfluorometry suggested that at least 50-70 percent of the proliferating blasts withdrew from proliferative activity after 2-3 days of culture. Morphologic studies demonstrated that lymphoblasts persisted as such for 1-2 days in vitro and then matured into typical plasma cells. Many of the blastprogeny had small nuclei and considerable basophilic cytoplasm on Giemsa-stained cell smears; abundant rough endoplasmic reticulum by electron microscopy; and readily detectable cytoplasmic Ig by immunocytochemistry. Reversion of blasts to small lymphocytes could not be detected; however, some blasts persisted even after 3 days of culture. The viability of the cultured lymphoblast was followed by initially tagging the cells with [(3)H]thymidine as well as several other techniques. Little cell death was documented during the first day of culture. The number of labeled progeny increased twofold whereas the grain count halved. But 40- 50 percent of the cell-associated label was lost during each of the second and third days, and fewer labeled progeny than predicted by grain count dilution were identified. The culture medium could not be implicated in this loss of lymphoblast progeny, and we suggest that the maturation of the lymphoblast to a short-lived plasma cell was responsible. Therefore mitogen-stimulated B blasts seem to mature into typical plasma cells after just two cycles of cell division. The plasma cells resemble those produced in situ during an immune response in their cytologic features, withdrawal from active proliferative activity, and short life-span.
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PMID:Mouse spleen lymphoblasts generated in vitro. Their replication and differentiation in vitro. 56 90

When large proportions of B lymphocytes from the murine spleen are stimulated in vitro by bacterial lipopolysaccharide (LPS) B lymphoblasts with small amounts of intracellular immunoglobulin (Ig) and plasmablasts with large amounts of intracellular Ig concomitantly proliferate. It is likely that B lymphocytes are heterogeneous and LPS activates B cells to express their predetermined functional capacity since bromodeoxyuridine does not inhibit the initiation of Ig synthesis in plasmablasts, and Ig synthesis starts before these cells complete their first mitosis. The results suggest that LPS is a potent polyclonal activator (of a B-cell subset) but it is not a differentiation factor in the sense that it is unable to determine whether its target cell develops extensive endoplasmic reticulum or follows a different pathway. The results do not exclude that modulation of B cells' genetic programming might take place during T cell-dependent B-lymphocyte activation. The observed B-cell heterogeneity offers a possible explanation for the concomitant emergence of B memory cells and antibody producers during the early phase of immune responses in vivo.
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PMID:Patterns of B-lymphocyte gene expression elicited by lipopolysaccharide mitogen. 108 14

The role that inflammatory cytokines may play in the life cycle of the hepatitis B virus and in the pathogenesis of its associated liver disease has not been carefully delineated. In this report, we demonstrate that bacterial lipopolysaccharide, a potent inducer of inflammatory cytokines in vivo, causes a severe acute liver disease in transgenic mice whose hepatocytes produce the hepatitis B virus large envelope polypeptide and retain HBsAg within the endoplasmic reticulum. In contrast, 100-fold higher doses of bacterial lipopolysaccharide do not induce liver cell injury in nontransgenic littermate controls or in transgenic mice whose hepatocytes secrete HBsAg rather than retain it. Coincident with the hepatocellular injury and the influx of inflammatory cells into the liver, a marked reduction occurs in the intrahepatic content of hepatitis B virus steady-state messenger RNA, thereby confirming the selectivity of this process for the HBsAg-positive hepatocyte. Bacterial lipopolysaccharide-induced hepatocellular injury appears to be principally mediated by interferon-gamma because it can be markedly reduced by the prior administration of neutralizing interferon-gamma-specific monoclonal antibodies and because recombinant interferon-gamma is also selectively cytotoxic for the HBsAg-positive transgenic hepatocyte in vivo. Tumor necrosis factor-alpha is also involved in this process because bacterial lipopolysaccharide-induced liver cell injury is significantly reduced by tumor necrosis factor-alpha specific monoclonal antibodies. The role of tumor necrosis factor-alpha in bacterial lipopolysaccharide-induced liver cell injury is less clear than interferon-gamma, however, because unlike interferon-gamma it is also toxic for nontransgenic hepatocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:HBsAg retention sensitizes the hepatocyte to injury by physiological concentrations of interferon-gamma. 150 8

Mott cells are a variant form of plasma cell in which the immunoglobulin (Ig), rather than being secreted, accumulates in rough endoplasmic reticulum-derived vesicles called Russell bodies. We have examined the molecular cause of this defect and the in vivo origin of IgM Mott cells. Our examination of the Ig variable region gene sequences of two IgM Mott hybridomas derived from C.B-20 Ly-1 B cells showed all to be germ line. In a series of mix and match transfection experiments, the Mott phenotype was only reconstituted when the original Mott specificity was expressed as an IgM, suggesting that both the specificity and the isotype were critical to the formation of Russell bodies. Based on our finding that Russell body formation was dependent on the Ig isotype being IgM, we suggest that the Mott phenotype is apparent only after differentiation of B cells into plasma cells and that probably the major cause of the IgM Mott phenotype is low-affinity interaction of the Mott Ig with some as yet unknown intracellular component(s) being stabilized by the intrinsic high avidity of the pentameric secreted form of IgM. Consistent with this proposal was the finding that after in vitro lipopolysaccharide (LPS) stimulation of sorted Ly-1 B cells derived from C.B-20 mice, Mott cells represented up to 5% of the IgM plasma cells in the culture. LPS stimulation of conventional B cells also induced the appearance of IgM Mott cells, but at the much reduced level of 0.1%, suggesting that the major, if not the only, source of Mott cells in vivo is the Ly-1 B cell population. A possible causal relationship between the elevated frequency of Mott cells in the Ly-1 B cell-derived LPS blasts and the repertoire selection inherent in the development of these B cells is discussed.
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PMID:An explanation for the defect in secretion of IgM Mott cells and their predominant occurrence in the Ly-1 B cell compartment. 153 87

There are large developmental increases in the rates of dolichol-linked oligosaccharide synthesis and protein N-glycosylation when resting murine splenic B lymphocytes are activated by bacterial lipopolysaccharide (LPS). These in vivo and in vitro studies were carried out to investigate the underlying biochemical mechanisms involved in the dramatic increase in the rate of oligosaccharide-lipid biosynthesis in LPS-stimulated B cells. Metabolic labelling experiments showed that the rate of synthesis of N-acetyl-glucosaminylpyrophosphoryldolichol (GlcNAc-P-P-Dol), mannosylphosphoryldolichol (Man-P-Dol) and glucosylphosphoryldolichol (Glc-P-Dol) increased 4- to 15-fold between 20 and 40 h after exposure to LPS. When the glycosyltransferase activities catalysing the formation of the three dolichol-bound monosaccharides were assayed in vitro with endoplasmic reticulum (ER)-enriched fractions, the initial rates were found to be elevated 4-fold prior to the major increases in oligosaccharide-lipid intermediate biosynthesis observed in vivo. Based on kinetic analyses, the higher enzyme activities were due to an increase in the amount of the three glycosyltransferases in activated cells. The time courses for elevated cellular content and rate of synthesis of guanosine-diphosphomannose (GDP)-Man corresponded to the developmental increase in oligosaccharide-lipid synthesis. The kinetics and magnitude of the induction of oligosaccharide-lipid synthesis were similar whether the initial rates were calculated on the basis of [2-3H]mannose-labelling or the specific activity of the GDP-[2-3H]mannose pool.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Expression of dolichol-linked saccharide intermediate synthesis during the development of B lymphocytes. 172 46

An earlier report from this laboratory documented a substantial increase in the rates of dolichol-linked oligosaccharide intermediate synthesis and protein N-glycosylation in purified murine splenic B lymphocytes (B cells) activated by treatment with bacterial lipopolysaccharide (LPS). In this study the developmental patterns for the induction of lipid-mediated protein N-glycosylation, membrane protein, and phosphatidylcholine (PC) biosynthesis were compared during the proliferative response of B cells to LPS. By electron microscopy it could be seen that a distinct endoplasmic reticulum (ER) network began to develop by 24-48 h after exposure of the purified B cells to LPS. The rate of synthesis of membrane protein increased markedly during the first 10 h after activation, reaching a maximum at 30-40 h. The induction of protein N-glycosylation was delayed slightly relative to membrane protein synthesis, with glycoprotein synthesis increasing sharply approximately 20 h after activation. When phospholipid synthesis was monitored by measuring [CH3-3H]choline incorporation into PC, the rate of labeling increased slowly during the first 35 h, but more substantially between 35 and 90 h. The incorporation of labeled choline into PC was drastically reduced by 5'-deoxy-5'-isobutylthio-3-deazaadenosine, an inhibitor of CDP-choline synthesis, indicating that the incorporation of radiolabeled choline is primarily a measurement of the rate of de novo synthesis of PC. In vitro assays revealed that while choline kinase activity was virtually unchanged, CDP-choline synthetase activity increased gradually throughout the activation period. Diacylglycerol cholinephosphotransferase activity, an ER-associated enzyme, was present at low levels between 0 and 35 h, but increased fivefold between 35 and 90 h. On the basis of the developmental patterns for the rates of protein N-glycosylation, membrane protein insertion, and PC biosynthesis determined by metabolic labeling experiments, we tentatively conclude that all of the ER-associated membrane proteins involved in these biosynthetic processes are not induced concurrently during the activation of B cells by LPS.
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PMID:Biogenesis of the endoplasmic reticulum in activated B lymphocytes: temporal relationships between the induction of protein N-glycosylation activity and the biosynthesis of membrane protein and phospholipid. 184 17

We attempted in this experiment to culture epithelioid cells isolated from granuloma induced in the lung of female rabbits that had been injected intravenously with Freund's complete adjuvant. The morphologic findings of isolated cells included abundant rough-surfaced endoplasmic reticulum, mitochondria, Golgi complexes, electron-dense lysosomes, and numerous cytoplasmic processes on the cell surface. Enzymatically these cells were positive for acid alpha-naphthyl acetate and beta-galactosidase staining. These findings coincided with the expected morphologic and enzymatic characteristics of epithelioid cells examined in vivo. Cells isolated from this granuloma are thought to be more than 86% epithelioid cells. Additionally, 14.4 +/- 4.3% of the epithelioid cells showed phagocytosis of latex beads, low when compared with the 83.9 +/- 5.2% value of alveolar macrophages obtained from rabbits injected with adjuvant 4 weeks before sacrifice. The isolated epithelioid cells were incubated for 24 h without decrease in cell population. Their culture supernatants showed 1.86 +/- 0.38 units/ml of angiotensin-converting enzyme (ACE) activity, which was inhibited by cycloheximide. The culture supernatants also showed interleukin-1 (IL-1) activity levels of 6411 +/- 914 cpm without lipopolysaccharide (LPS) stimulation. This increased to 21,766 +/- 3026 cpm with LPS stimulation. In view of these results, we believe it is possible to incubate epithelioid cells for up to 24 h during which time they will produce ACE and IL-1 in the culture supernatants.
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PMID:In vitro angiotensin-converting enzyme and interleukin-1 production by epithelioid cells isolated from induced rabbit lung granuloma. 217 24

The murine B-cell lymphoma CH12, like many other murine cells, expresses intracisternal A-type particles (IAPs). When CH12 cells are treated with lipopolysaccharide, the cells differentiate and secrete immunoglobulin M. The expression of IAP genes was also increased, in parallel with the increased expression of immunoglobulin genes. The amount of IAP mRNA increased within 48 h of lipopolysaccharide treatment and reached a level fivefold higher than that in unactivated CH12 cells. The two major IAP transcripts (7.2 and 5.4 kilobases) were induced to similar extents. The increased level of mRNA was reflected in higher levels of the major IAP structural protein p70, whose abundance increased 3.6-fold. The number of IAP particles per cell also increased upon activation of CH12, from 67 in nonsecreting CH12 to 290 in secreting cells. All of the IAPs were confined to the cisternae of the endoplasmic reticulum (ER), regardless of the differentiation state of the cell. Accompanying the induction of p70 was the induction of the related IAP polypeptide p102. A third viral polypeptide, p120, was also made in CH12; its abundance was almost unchanged. Localization of the IAP proteins on ultrathin frozen sections showed that most were assembled into particles in the ER. However, there were small pools of unassembled proteins both in the ER and on the plasma membrane. p70 and p120 could be detected, by iodination, on the surfaces of both secreting and nonsecreting CH12 cells. Unlike p70 and p120, p102 did not seem to be membrane associated. Taken together, these observations show that IAP expression is regulated developmentally in B lymphocytes. Also, these observations point to possible interactions between IAP genes and other cellular genes.
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PMID:Expression of intracisternal A-type particles is increased when a B-cell lymphoma differentiates into an immunoglobulin-secreting cell. 249 59

Human peripheral blood monocytes (Mo) synthesize prostaglandin E2 (PGE2) when activated with lipopolysaccharide (LPS). This production is strongly enhanced by the addition of supernatant from phytohaemagglutinin (PHA)-activated T cells. To evaluate the factor(s) responsible for this enhancement we studied the effect of several cytokines on the PGE2 metabolism. Recombinant interleukin-1 (IL-1) or recombinant IL-2 strongly enhanced PGE2 synthesis in LPS-stimulated Mo cultures, whereas recombinant interferon-gamma (IFN-gamma) partially inhibited its production. To see whether the effect of IL-2 on Mo was due to the presence of IL-2 receptor (IL-2R) on the cell surface, flow cytometric analysis and electron microscopy were used to investigate IL-2R expression in unstimulated and stimulated Mo. Stimulated, but not resting, Mo displayed the p55 IL-2R chain on their cellular surface and associated with the polyribosomes of the rough endoplasmic reticulum in the cytoplasm. This finding strongly suggested that the p55 chain of the IL-2R was synthesized by activated Mo. To confirm this result, 125I-labelled IL-2 was bound under high- and low-affinity conditions and cross-linked to Mo cultured in the presence of LPS, IFN-gamma or IL-1. The cross-linked 125I-IL-2/IL-2R complexes were analysed by SDS-PAGE. Mo cultured with LPS, IFN-gamma and IL-1 expressed the p55 protein detected by low-affinity cross-linking, whereas only LPS-stimulated Mo displayed a barely detectable band with an apparent MW of 70,000 under high-affinity binding conditions. In addition, stimulated Mo were found capable of producing the soluble form of IL-2R. Finally, LPS-activated Mo only responded to the addition of IL-2 by an increase in PGE2 production, suggesting that the function of IL-2R on activated Mo is linked to the stimulus applied.
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PMID:The expression of functional IL-2 receptor on activated macrophages depends on the stimulus applied. 266 16


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